Presently, all the targets of clinically applied anti-virus drugs are viral proteins. The functioning mechanism of these drugs is to inhibit the replication of the virus or to block the invasion of the virus. The viruses are “moving targets”, they will perpetually vary themselves to elude the attack of the drugs. It is a world scale conundrum that the variations of viruses induced by the drugs targeting the viral proteins and resulting in the resistance to drugs. In the same way, the targets of the anti-AIDS virus drugs using currently in common clinic are the HIV viral proteins too. They will cause severe problem of the resistance to drugs and subsequently failure of the remedy. Multidrug therapy (MDT, cocktail therapy) can greatly decrease virus stock and retard the occurrence of resistance to drugs, however, still the occurrence of resistance to drugs will finally be inevasible. The newly marketed variety of drugs has possessed some advantages against the virus strains with resistance to drugs, nevertheless, as prolonged application in clinic, the resistance to drugs is still unavoidable. Therefore, it is a presently primary topic to tackle the problem of resistance to drugs.
Along with ever-deepening development of the researches on virology and cell biology, vast amount of research results demonstrated that the host cells universally form their own defending system against different pathologic viruses during the endless course of organic evolution, and the viruses form also specific antagonistic mechanism for their own to evade the inhibition effect from the host cells. Presently, the relationships of mutual dependence and antagonism between viruses and host cells, especially those relating to HIV-1 cytokines, have become the leading edge and most rapidly developing area in the researches of fundamentals and applications of medical chemistry.
Vif (virion infectivity factor) is the viral protein coded by HIV-1 genome, it plays a key role in HIV-1 replication and infection. Recent researches have demonstrated that hA3G related closely to the biological function of Vif. hA3G is a kind of RNA/DNA editing enzyme expressed in human lymphocytes and is a member of the APOBEC protein superfamily. APOBEC3G belongs to APOBEC family. The most recent results of research showed that APOBEC3G protein may induce G to A hypermutability of HIV-1 virus genome and inhibit virus replication with high efficiency. It is an anti-virus cellular factor naturally produced in host cells.
Anti-virusantiviral screening researches using hA3G/Vif interaction as target demonstrated that 3-amino benzoyl derivatives have the activity to inhibit the interaction process of hA3G/Vif and the replication of the viruses. These compounds put forward in this invention and their functions have not been found in the literature in China and abroad up to now. The development of new anti-virus compounds aiming at a newnovel drug target hA3G may make a breakthrough at solving the problem about HIV with resistance to drugs, thereby can provide more effective new anti-virusantiviral drugs for clinic.
A main object of this invention is to screen out a new kind of anti-virus compounds and their pharmaceutically salts aiming at hA3G/Vif interaction as the target via the structure-activity research on a group of amino benzoyl derivatives. Not only this kind of compounds inhibits the hA3G/Vif conjugation interaction binding, but it possesses significant anti-virus activity.